Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity.

Cellular recovery after prolonged warm ischaemia of the whole body.

After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges.

Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells.

The hippocampal-entorhinal system supports cognitive functions, has lifelong neurogenic capabilities in many species, and is selectively vulnerable to Alzheimer's disease. To investigate neurogenic potential and cellular diversity, we profiled single-nucleus transcriptomes in five hippocampal-entorhinal subregions in humans, macaques, and pigs. Integrated cross-species analysis revealed robust transcriptomic and histologic signatures of neurogenesis in the adult mouse, pig, and macaque but not humans.

Regulation of prefrontal patterning and connectivity by retinoic acid.

The prefrontal cortex (PFC) and its connections with the mediodorsal thalamus are crucial for cognitive flexibility and working memory and are thought to be altered in disorders such as autism and schizophrenia. Although developmental mechanisms that govern the regional patterning of the cerebral cortex have been characterized in rodents, the mechanisms that underlie the development of PFC-mediodorsal thalamus connectivity and the lateral expansion of the PFC with a distinct granular layer 4 in primates remain unknown. Here we report an anterior (frontal) to posterior (temporal), PFC-enriched gradient of retinoic acid, a signalling molecule that regulates neural development and function, and we identify genes that are regulated by retinoic acid in the neocortex of humans and macaques at the early and middle stages of fetal development.

Brain vulnerability and viability after ischaemia.

The susceptibility of the brain to ischaemic injury dramatically limits its viability following interruptions in blood flow. However, data from studies of dissociated cells, tissue specimens, isolated organs and whole bodies have brought into question the temporal limits within which the brain is capable of tolerating prolonged circulatory arrest. This Review assesses cell type-specific mechanisms of global cerebral ischaemia, and examines the circumstances in which the brain exhibits heightened resilience to injury.

Chemerin Blood Levels are Associated with MRI Measured Volumes of Abdominal Adipose Tissue Compartments and Lifestyle Choices.

Obesity is a low-grade chronic inflammatory state, in which a cytokine chemerin with its immunometabolic modulation has an important role. We aimed to study in a healthy population relationships between serum chemerin levels, lifestyle choices and magnetic resonance imaging (MRI) assessed volumes of abdominal visceral (VAT) and subcutaneous (SAT) adipose tissues, which have different cytokine expression profiles. Overall, 73 healthy participants undertook lifestyle questionnaire and underwent anthropometric measurements along with MRI scanning of abdominal SAT and VAT.

Transcardial gradient of adiponectin, interleukin-6 and tumor necrosis factor-α in overweight coronary artery disease patients.

Background: Obesity is associated with coronary artery disease (CAD), where epicardial adipose tissue (EAT) express proatherogenic cytokines (i.e., interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)) and decreases production of beneficial adiponectin.